Isatoic anhydride explained

Isatoic anhydride is an organic compound derived from anthranilic acid. A white solid, it is prepared by reaction of anthranilic acid with phosgene.^[1]

Reactions

Hydrolysis gives carbon dioxide and anthranilic acid. Alcoholysis proceeds similarly, affording the ester:

C₆H₄C₂O₃NH + ROH → C₆H₄(CO₂R)(NH₂) + CO₂Amines also effect ring-opening. Active methylene compounds and carbanions replace oxygen giving hydroxyquinolinone derivatives. Deprotonation followed by alkylation gives the N-substituted derivatives. Sodium azide gives the benzimidazolone via the isocyanate.^[2] Isatoic anhydride is used as a blowing agent in the polymer industry, an application that exploits its tendency to release CO₂.

Uses

Isatoic anhydride has been used as a precursor for the synthesis of methaqualone^[3] and related 4-quinazolinone-based pharmaceutical drugs, including:

1. Tioperidone
2. Tranilast
3. Pelanserin
4. Diproqualone
5. Antrafenine
6. SJ-733
7. Nicafenine
8. Molinazone
9. Cloperidone
10. SGB 1534

References

1. Org. Synth.. 1947. 27. 45. 10.15227/orgsyn.027.0045. Isatoic anhydride. E. C. Wagner . Marion F. Fegley. .
2. The Chemistry of Isatoic Anhydride. Coppola, Gary M.. Synthesis. 1980. 7. 7 . 505–36. 10.1055/s-1980-29110.
3. A survey of reported syntheses of methaqualone and some positional and structural isomers . Etienne F. van Zyl . Forensic Sci. Int. . 122 . 142–149 . 2001 . 2–3 . 10.1016/S0379-0738(01)00484-4 . 11672968 .